scholarly journals A novel PDX modeling strategy and its application in metabolomics study for malignant pleural mesothelioma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhongjian Chen ◽  
Chenxi Yang ◽  
Zhenying Guo ◽  
Siyu Song ◽  
Yun Gao ◽  
...  

Abstract Background Malignant pleural mesothelioma (MPM) is a rare and aggressive carcinoma located in pleural cavity. Due to lack of effective diagnostic biomarkers and therapeutic targets in MPM, the prognosis is extremely poor. Because of difficulties in sample extraction, and the high rate of misdiagnosis, MPM is rarely studied. Therefore, novel modeling methodology is crucially needed to facilitate MPM research. Methods A novel patient-derived xenograft (PDX) modeling strategy was designed, which included preliminary screening of patients with pleural thickening using computerized tomography (CT) scan, further reviewing history of disease and imaging by a senior sonographer as well as histopathological analysis by a senior pathologist, and PDX model construction using ultrasound-guided pleural biopsy from MPM patients. Gas chromatography-mass spectrometry-based metabolomics was further utilized for investigating circulating metabolic features of the PDX models. Univariate and multivariate analysis, and pathway analysis were performed to explore the differential metabolites, enriched metabolism pathways and potential metabolic targets. Results After screening using our strategy, 5 out of 116 patients were confirmed to be MPM, and their specimens were used for modeling. Two PDX models were established successfully. Metabolomics analysis revealed significant metabolic shifts in PDX models, such as dysregulations in amino acid metabolism, TCA cycle and glycolysis, and nucleotide metabolism. Conclusions To sum up, we suggested a novel modeling strategy that may facilitate specimen availability for MM research, and by applying metabolomics in this model, several metabolic features were identified, whereas future studies with large sample size are needed.

2021 ◽  
Author(s):  
Zhongjian Chen ◽  
Chenxi Yang ◽  
Zhenying Guo ◽  
Siyu Song ◽  
Yun Gao ◽  
...  

Abstract Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive carcinoma located in pleural cavity. Due to lack of effective diagnostic biomarkers and therapeutic targets in MPM, the prognosis is extremely poor. Because of difficulties in sample extraction, and the high rate of misdiagnosis, MPM is rarely studied. Therefore, novel modeling methodology is crucially needed to facilitate MPM research. Methods:A novel PDX modeling strategy was designed, which included preliminary screening of patients with pleural thickening using computerized tomography (CT) scan, further reviewing history of disease and imaging by a senior sonographer as well as histopathological analysis by a senior pathologist, and then patient-derived xenograft (PDX) model construction using ultrasound-guided pleural biopsy from MPM patients. Gas chromatography–mass spectrometry-based metabolomics was further utilized for investigating circulating metabolic features of the PDX models. Univariate and multivariate analysis, and pathway analysis were performed to explore the differential metabolites, enriched metabolism pathways and potentially metabolic targets. Results:After screening using our strategy, 5 out of 116 patients were confirmed to be MPM, and their specimens were used for modeling. Two PDX models were established successfully. Metabolomics analysis revealed significant metabolic shifts in PDX models, such as dysregulations in amino acid metabolism, TCA cycle and glycolysis, and nucleotide metabolism. Conclusions:To sum up, we suggested a novel modeling strategy that may facilitate specimen availability for MM research, and by application of metabolomics on this model, several metabolic features were identified, whereas future studies with large sample size are needed.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Declan C. Murphy ◽  
Alexander Mount ◽  
Fiona Starkie ◽  
Leah Taylor ◽  
Avinash Aujayeb

AbstractObjectivesThe National Mesothelioma Audit 2020 showed Northumbria to have low rates of histopathological confirmation, treatment and one-year survival rates for malignant pleural mesothelioma (MPM). We hypothesized that an internal analysis over a 10-year period provides valuable insights into presentation, diagnosis, treatment and outcomes.MethodsA single-centre retrospective case series of all confirmed MPM patients between 1 January 2009 and 31 December 2019 was performed. Demographics, clinical, radiological and histopathological characteristics and outcomes were collected. Statistical analysis was performed using SPSS V26.0.ResultsA total of 247 patients had MPM. About 86% were male, mean age 75.7 years. Dyspnoea (77.4%) and chest pain (38.5%) were commonest symptoms. 64.9 and 71.4% had pleural thickening and effusion, respectively. About 86.8% had at least one attempt to obtain a tissue biopsy, but histopathological confirmation in only 108 (43.7%). About 66.3% with PS 0 and 1 (62.7% of total cohort) had at least one anti-cancer therapy. Death within 12 months was associated with disease progression within 6 months (p≤0.001). Chemotherapy (p≤0.001) and epithelioid histological subtype (p=0.01) were protective.ConclusionsThis study confirms known epidemiology of MPM, demonstrates variability in practices and highlights how some NMA recommendations are not met. This provides the incentive for a regional mesothelioma multi-disciplinary meeting.


2017 ◽  
Vol 2017 ◽  
pp. 1-5
Author(s):  
Reiko Ideguchi ◽  
Kazuto Ashizawa ◽  
Saori Akashi ◽  
Michiko Shindo ◽  
Kazunori Minami ◽  
...  

We herein report two cases of malignant pleural mesothelioma with marked lymphangiosis. The patients included a 68-year-old man and a 67-year-old man who both had a history of exposure to asbestos. Computed tomography (CT) on admission showed pleural effusion with pleural thickening. In both cases, a histopathological examination of the pleura confirmed the diagnosis of epithelioid malignant mesothelioma. They received chemotherapy, but the treatment was only palliative. The chest CT assessments during admission revealed marked pleural effusion and mediastinal lymphadenopathy. CT also showed a consolidative mass with bronchovascular bundle and septal thickening in the lungs suggesting pulmonary parenchymal involvement and the lymphangitic spread of the tumor. These CT findings mimicked lung cancer with pleuritis and lymphangitic carcinomatosis. Autopsy was performed in both cases. Macroscopically, the tumor cells infiltrated the lung with the marked lymphatic spread of the tumor. Microscopy also revealed that the tumor had invaded the pulmonary parenchyma with the marked lymphatic spread of the tumor. Although this growth pattern is unusual, malignant pleural mesothelioma should be considered as the differential diagnosis, especially in patients with pleural lesions.


2017 ◽  
Vol 50 (6) ◽  
pp. 1700919 ◽  
Author(s):  
Kevin Lamote ◽  
Matthijs Vynck ◽  
Olivier Thas ◽  
Joris Van Cleemput ◽  
Kristiaan Nackaerts ◽  
...  

Malignant pleural mesothelioma (MPM) is predominantly caused by asbestos exposure and has a poor prognosis. Breath contains volatile organic compounds (VOCs) and can be explored as an early detection tool. Previously, we used multicapillary column/ion mobility spectrometry (MCC/IMS) to discriminate between patients with MPM and asymptomatic high-risk persons with a high rate of accuracy. Here, we aim to validate these findings in different control groups.Breath and background samples were obtained from 52 patients with MPM, 52 healthy controls without asbestos exposure (HC), 59 asymptomatic former asbestos workers (AEx), 41 patients with benign asbestos-related diseases (ARD), 70 patients with benign non-asbestos-related lung diseases (BLD) and 56 patients with lung cancer (LC).After background correction, logistic lasso regression and receiver operating characteristic (ROC) analysis, the MPM group was discriminated from the HC, AEx, ARD, BLD and LC groups with 65%, 88%, 82%, 80% and 72% accuracy, respectively. Combining AEx and ARD patients resulted in 94% sensitivity and 96% negative predictive value (NPV). The most important VOCs selected were P1, P3, P7, P9, P21 and P26.We discriminated MPM patients from at-risk subjects with great accuracy. The high sensitivity and NPV allow breath analysis to be used as a screening tool for ruling out MPM.


2020 ◽  
Vol 26 (1) ◽  
pp. 95-103
Author(s):  
Akifumi Nakamura ◽  
Masaki Hashimoto ◽  
Hiroshi Kodama ◽  
Michiko Yuki ◽  
Nobuyuki Kondo ◽  
...  

2015 ◽  
Vol 8 (3) ◽  
pp. 439-446
Author(s):  
Daizo Yaguchi ◽  
Motoshi Ichikawa ◽  
Noriko Inoue ◽  
Daisuke Kobayashi ◽  
Akinobu Matsuura ◽  
...  

The patient experienced chest pain for about 7 months, but a diagnosis could not be made until after death. He was diagnosed with malignant sarcomatoid pleural mesothelioma on autopsy. In this case report, difficult aspects of the diagnosis are discussed. The 70-year-old Japanese man was a driver who transported ceramic-related products. Right chest pain developed in July 2013, but no abnormality was detected on a chest computed tomography (CT) performed in September 2013, and the pain was managed as right intercostal neuralgia. A chest CT performed in late October 2013 revealed a right pleural effusion, and the patient was referred to our hospital in early November 2013. Thoracentesis was performed, but the cytology was negative, and no diagnosis could be made. Close examination was postponed because the patient developed a subarachnoid hemorrhage. He underwent 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) after discharge from the neurosurgery department, and extensive right pleural thickening and 18F-FDG accumulation in this region were observed. Based on these findings, malignant pleural mesothelioma was suspected, and a thoracoscopy was performed under local anesthesia in early December 2013, but no definite diagnosis could be made. The patient selected best supportive care and died about 7 months after the initial development of right chest pain. The disease was definitively diagnosed as malignant sarcomatoid pleural mesothelioma by a pathological autopsy. When chronic chest pain of unknown cause is observed and past exposure to asbestos is suspected, actions to prevent delay in diagnosis should be taken, including testing for suspicion of malignant pleural mesothelioma.


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